A novel method of detection of early-stage keratoconus is proposed and is needed to respond to emerging treatment options for this disease. The ability to stop the progression of this disease at its early stage is highly desired, and this now appears possible. Required for this goal is a method to provide low-cost (below $5,000) and sensitive measurements and detection of early-stage keratoconus for the population of greatest susceptibility. The second stimulus for this research also derives from increased options for corrections of vision defects. Undesired outcomes can result from normally successful laser surgery if corneal material is removed from the eyes of patients with undetected forme fruste keratoconus (FFKC). Alternative detection and diagnostic options of this condition is needed to continue the advance of this vision-improving surgical therapy. This proposed study combines physical and medical sciences to satisfy this need for screening for FFKC and early-stage KC in both clinical and non-clinical applications. A cutting-edge technique of personalized eye modeling will be utilized with contemporary clinical wavefront, topography, and ocular biometry data to provide high-fidelity optical models of FFKC and KC eyes. Using this capability, realistic instrument measurement simulations will guide the optimal design of a low-cost device to approach the high-sensitivity detection. This cost-effective method uses multi-eccentric, multi-meridian, adaptive photorefraction (APR) to observe and measure the double-pass wavefront of the FFKC. A sequence of narrow-band, near-infrared (NIR) LED sources that are imbedded on a 2-dimensional plane will be used with typical commercial multi- frame camera. Low power NIR sources will enable non-mydriatic examination covering the larger scotopic visual zone of patients in a darkened testing environment. Quantitative image analysis will be developed from both the clinically measured and the predicted performance on subjects. Digital registration facilitates computer-aided diagnosis (CADx) and extraction of the image's maximum information content, and it enables telemedicine applications. Together, the proposed optical design and hardware engineering and the auto- analysis features provide a promising device and method that could be utilized to provide a medical service in a very broad range of clinical environments. PUBLIC HEALTH RELEVANCE Collaboration of physical and medical sciences will be achieved to provide a method of detection of early-stage keratoconus. Optical computations will be used in conjunction with clinical patient data to realize the optimal design and quantitative predictions and clinical performance results. The device and analysis method will be low-cost, both user- and subject- friendly and suitable for screening of clinical and larger population subjects.